Activation of integrated provirus requires histone acetyltransferase. p300 and P/CAF are coactivators for HIV-1 Tat

• Published in: The Journal of biological chemistry Vol. 273; no. 38; pp. 24898 - 24905
• Main Authors: Benkirane, M, Chun, R F, Xiao, H, Ogryzko, V V, Howard, B H, Nakatani, Y, Jeang, K T
• Format: Journal Article
• Language: English
• Published: United States 18.09.1998
• Subjects: 3T3 Cells; Acetyltransferases - metabolism; Animals; Binding Sites; Cell Cycle Proteins - metabolism; Chromatin - genetics; Chromatin - physiology; Cloning, Molecular; Gene Products, tat - genetics; Gene Products, tat - isolation & purification; Gene Products, tat - metabolism; HeLa Cells; Histone Acetyltransferases; HIV Long Terminal Repeat; HIV-1 - enzymology; HIV-1 - genetics; HIV-1 - physiology; Human immunodeficiency virus 1; Humans; Life Cycle Stages; Mice; p300-CBP Transcription Factors; Proviruses - genetics; Proviruses - physiology; Recombinant Fusion Proteins - isolation & purification; Recombinant Fusion Proteins - metabolism; Saccharomyces cerevisiae Proteins; Sequence Deletion; tat Gene Products, Human Immunodeficiency Virus; Transcription Factors; Virus Integration
• ISSN: 0021-9258
• DOI: 10.1074/jbc.273.38.24898

A unique aspect of the retrovirus life cycle is the obligatory integration of the provirus into host cell chromosomes. Unlike viruses that do not integrate, retroviruses must conserve an ability to activate transcription from a chromatin context. Human immunodeficiency virus (HIV)-1 encodes an unusual and an unusually potent transcriptional transactivator, Tat, which binds to a nascent viral leader RNA, TAR. The action of Tat has been well studied in various reductive model systems; however, the physiological mechanism through which Tat gains access to chromatin-associated proviral long terminal repeats (LTRs) is not understood. We show here that a nuclear histone acetyltransferase activity associates with Tat. Intracellularly, we found that Tat forms a ternary complex with p300 and P/CAF, two histone acetyltransferases (HATs). A murine cell defect in Tat transactivation of the HIV-1 LTR was linked to the reduced abundance of p300 and P/CAF. Thus, overexpression of p300 and P/CAF reconstituted Tat transactivation of the HIV-1 LTR in NIH3T3 cells to a level similar to that observed for human cells. By using transdominant p300 or P/CAF mutants that lack enzymatic activity, we delineated a requirement for the HAT component from the latter but not the former in Tat function. Finally, we observed that Tat-associated HAT is preferentially important for transactivation of integrated, but not unintegrated, HIV-1 LTR.